Diadenosine pentaphosphate is more potent than ATP at P2X receptors in isolated rat vagus nerve

The effects of diadenosine pentaphosphate (Ap5A), diadenosine tetraphosphate (Ap4A), alpha,beta-methyleneATP (alpha,beta-meATP), and ATP were studied on the excitability of unmyelinated axons in isolated rat vagus nerve by means of a computerized threshold tracking technique. All purinergic compounds produced an increase in excitability, however, only the effects of alpha,beta-meATP and of Ap5A were strongly reduced by 2'- (or 3') -O-(2,4,6-trinitrophenyl)-ATP (TNP-ATP), a selective blocker for P2X1, P2X3, and heteromeric P2X2/3 receptors. The rank order of potency for TNP-ATP-sensitive excitation was determined as follows (30 microM each): alpha,beta-meATP >Ap5A >> Ap4A = ATP. These data suggest that Ap5A might be an important naturally occurring agonist for P2X receptors at the axonal membrane of unmyelinated, including nociceptive, nerve fibres.